PMID- 21700931
OWN - NLM
STAT- MEDLINE
DCOM- 20111003
LR  - 20201209
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 109
IP  - 4
DP  - 2011 Aug 5
TI  - Caloric restriction primes mitochondria for ischemic stress by deacetylating 
      specific mitochondrial proteins of the electron transport chain.
PG  - 396-406
LID - 10.1161/CIRCRESAHA.111.243097 [doi]
AB  - RATIONALE: Caloric restriction (CR) confers cardioprotection against 
      ischemia/reperfusion injury. However, the exact mechanism(s) underlying 
      CR-induced cardioprotection remain(s) unknown. Recent evidence indicates that 
      Sirtuins, NAD(+)-dependent deacetylases, regulate various favorable aspects of 
      the CR response. Thus, we hypothesized that deacetylation of specific 
      mitochondrial proteins during CR preserves mitochondrial function and attenuates 
      production of reactive oxygen species during ischemia/reperfusion. OBJECTIVE: The 
      objectives of the present study were (1) to investigate the effect of CR on 
      mitochondrial function and mitochondrial proteome and (2) to investigate what 
      molecular mechanisms mediate CR-induced cardioprotection. METHODS AND RESULTS: 
      Male 26-week-old Fischer344 rats were randomly divided into ad libitum-fed and CR 
      (40% reduction) groups for 6 months. No change was observed in basal 
      mitochondrial function, but CR preserved postischemic mitochondrial respiration 
      and attenuated postischemic mitochondrial H(2)O(2) production. CR decreased the 
      level of acetylated mitochondrial proteins that were associated with enhanced 
      Sirtuin activity in the mitochondrial fraction. We confirmed a significant 
      decrease in the acetylated forms of NDUFS1 and cytochrome bc1 complex Rieske 
      subunit in the CR heart. Low-dose resveratrol treatment mimicked the effect of CR 
      on deacetylating them and attenuated reactive oxygen species production during 
      anoxia/reoxygenation in cultured cardiomyocytes without changing the expression 
      levels of manganese superoxide dismutase. Treatment with nicotinamide completely 
      abrogated the effect of low-dose resveratrol. CONCLUSIONS: These results strongly 
      suggest that CR primes mitochondria for stress resistance by deacetylating 
      specific mitochondrial proteins of the electron transport chain. Targeted 
      deacetylation of NDUFS1 and/or Rieske subunit might have potential as a novel 
      therapeutic approach for cardioprotection against ischemia/reperfusion.
FAU - Shinmura, Ken
AU  - Shinmura K
AD  - Division of Geriatric Medicine, Department of Internal Medicine, Keio University 
      School of Medicine, Tokyo, Japan. shimmura@sc.itc.keio.ac.jp
FAU - Tamaki, Kayoko
AU  - Tamaki K
FAU - Sano, Motoaki
AU  - Sano M
FAU - Nakashima-Kamimura, Naomi
AU  - Nakashima-Kamimura N
FAU - Wolf, Alexander M
AU  - Wolf AM
FAU - Amo, Taku
AU  - Amo T
FAU - Ohta, Shigeo
AU  - Ohta S
FAU - Katsumata, Yoshinori
AU  - Katsumata Y
FAU - Fukuda, Keiichi
AU  - Fukuda K
FAU - Ishiwata, Kyoko
AU  - Ishiwata K
FAU - Suematsu, Makoto
AU  - Suematsu M
FAU - Adachi, Takeshi
AU  - Adachi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110623
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Antioxidants)
RN  - 0 (Electron Transport Chain Complex Proteins)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Permeability Transition Pore)
RN  - 0 (Rieske iron-sulfur protein)
RN  - 0 (Stilbenes)
RN  - 0U46U6E8UK (NAD)
RN  - 25X51I8RD4 (Niacinamide)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.6.99.3 (NADH Dehydrogenase)
RN  - EC 3.5.1.- (Sirtuins)
RN  - EC 7.1.1.8 (Electron Transport Complex III)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Acetylation
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Blotting, Western
MH  - *Caloric Restriction
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Electron Transport Chain Complex Proteins/*metabolism
MH  - Electron Transport Complex III/metabolism
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Mitochondria, Heart/drug effects/*metabolism
MH  - Mitochondrial Membrane Transport Proteins/metabolism
MH  - Mitochondrial Permeability Transition Pore
MH  - Myocardial Reperfusion Injury/metabolism/*prevention & control
MH  - Myocytes, Cardiac/drug effects/*metabolism
MH  - NAD/metabolism
MH  - NADH Dehydrogenase/metabolism
MH  - Niacinamide/pharmacology
MH  - *Oxidative Stress/drug effects
MH  - Proteomics
MH  - Rats
MH  - Rats, Inbred F344
MH  - Resveratrol
MH  - Sirtuins/*metabolism
MH  - Stilbenes/pharmacology
EDAT- 2011/06/28 06:00
MHDA- 2011/10/04 06:00
CRDT- 2011/06/25 06:00
PHST- 2011/06/25 06:00 [entrez]
PHST- 2011/06/28 06:00 [pubmed]
PHST- 2011/10/04 06:00 [medline]
AID - CIRCRESAHA.111.243097 [pii]
AID - 10.1161/CIRCRESAHA.111.243097 [doi]
PST - ppublish
SO  - Circ Res. 2011 Aug 5;109(4):396-406. doi: 10.1161/CIRCRESAHA.111.243097. Epub 
      2011 Jun 23.